大肠癌中DCC基因201密码子点突变的研究

Codon 201 point mutation of DCC gene in colorectal carcinoma

目的:探寻结直肠癌缺陷基因(DCC基因)201密码子在大肠癌中的突变规律。方法:采用等位基因特异性PCRAS-PCR结合SalⅠ酶切方法检测35例大肠癌组织及配对的癌旁粘膜DCC基因201密码子突变情况。结果:DCC基因201密码子纯合突变率大肠癌(40％)显著高于癌旁粘膜(2.8％),(P<0.05)。且与肿瘤侵袭深度、Dukes分期相关。至少有17例(49％)大肠癌与相应癌旁粘膜相比增获一个密码子突变。结论:201密码子是DCC基因热点突变部位,属大肠癌发生中的早期基因事件,201密码子突变与大肠癌侵袭、转移能力加强密切相关,可以作为大肠癌预后评估指标。

Objective: To explore the frequency of codon 201 point mutation of DCC gene in colorectal carcinoma (CRC) and the relationship between codon 201 mutation and biologic behavior of CRC. Methods: Samples of tumor tissues and matched adjacent normal colon mucosa tissues taken from 35 cases CRC patients were analyzed for codon 201 point mutation of DCC gene with allele-specific polymerase chain reaction- based restriction fragment length polymorphism methods. Results: The frequency of codon 201GLY (homozygous mutation) is significantly higher in tumor tissues (40%) than that of matched adjacent mucosa (2.8%). Statistic anal-ysis showed there was significantly correlation between mutation and tumor depth of invasion, as well as Dukes classification of CRC.at least 17 cases(49%) of the malignant tissues had acquired a new loss of wild type codon 201 compared with corresponding normal mucosa. Conclusion: The point mutation at codon 201 of DCC gene is an early premalignant events in CRC, and plays some role in invasion and metastasis of colorectal carcinoma. The codon 201 mutation of DCC gene appears to be a predictive indicators for local invasion and distant metastasis of CRC.